The 26-year-old from City of Shellharbour won more games than Xinyu Wang on Monday, but lost the match 7-5 1-6 6-4.
Perez, rated 352 in the world, twice looked in control against an opponent 274 places above her in the standings, taking the opening three games, then romping the second set.
But her first serve dropped off in the third set, managing to land just 50 per cent, and her Chinese opponent took advantage.
Perez's defeat left Daria Saville as the only Australian remaining in the singles draw. She faces former world No.1 and four-time grand slam champ Naomi Osaka in Tuesday's main fixture.
Elise Mertens won the first three games against Qiang Wang before Typhoon Nanmadol forced play to be suspended for 45 minutes while the roof at Ariake Coliseum was closed.
The Belgian then won the next three when they resumed in a 6-0 6-3 victory.
Her 30-year-old Chinese opponent managed to get to 3-3 in the second set but Mertens then won the last three games to advance to the second round. She now meets Claire Liu who progressed by beating fellow American Alison Riske-Amritraj 6-2 6-3.
Seventh-seeded Karolina Pliskova cruised past Isabella Shinikova 6-2 6-1 while Mexican qualifier Fernanda Contreras Gomez beat 2020 Australian Open champion Sofia Kenin 7-6 (9-7) 6-4.
China's Zhang Shuai beat Japanese wild-card entry Mai Hontama 6-0 6-3.
Former world No.1 Pliskova, who was the champion in Tokyo four years ago, had little trouble against the inconsistent Shinikova.
The Czech player said she was back on form after injuring herself at the start of the year.
"I missed the beginning of the season because I broke my arm, so I had a slower start to the season, but I feel like in the summer in America I was playing really good matches," Pliskova said.
"I reached the quarter-finals in the US Open and played some really good matches, so I think I'm in good shape and let's see how far I can go this week."
Kenin has seen her ranking plummet to 315 from a career-high of No.4. The American has failed to win her first match in 10 of the 12 tournaments she has played in 2022 after coming off a year plagued by injuries.
Zhang, who won in Lyon earlier this year and reached the last 16 at the US Open, will face second-seeded Caroline Garcia in the second round.
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